Objective : The aim of this study was to assess protective effects of Whangryonhaedoktang on the chronic mild stress (CMS) animal model of depression. Method : Male Sprague-Dawley rats were used for this study. The subjects were divided into 3 groups (CMS-drug group: Whangryonhaedoktang was administered during CMS procedure, CMS-vehicle: water was administered during CMS procedure, normal control group: without CMS procedure). After 4 weeks of CMS procedure, Morris water maze (MWM) test and open field test were executed and tyrosine hydroxylase (TH) was measured in ventral tegmental area (VTA) and locus coeruleus (LC) of rat brain. Result : 1. CMS procedure induced defects of spatial learning in early period of MWM test. 2. CMS Whangryonhaedoktang group showed shorter escape latency in comparison with CMS control group in MWM test on the first day of the test. 3. CMS Whangryonhaedoktang group and CMS control group showed no significant difference of activities and emotional behaviors in comparison with normal control group in open field test. 4. CMS Whangryonhaedoktang group showed significant inhibition effects of TH expression in VTA and LC areas in comparison with CMS control group. Conclusion : These results suggest that Whangryonhaedoktang may have inhibition effects to early period defects of spatial learning and protective antidepressant effects in CMS model rats.